title: Genetic and biochemical markers of hydroxyurea therapeutic response in sickle cell anemia.
abstract: BACKGROUND
  Sickle cell anemia (SCA) presents a complex pathophysiology which can be affected by a number of modifying factors, including genetic and biochemical ones. In Brazil, there have been no studies verifying βS-haplotypes effect on oxidative stress parameters. This study evaluated βS-haplotypes and Hb F levels effects on oxidative stress markers and their relationship with hydroxyurea (HU) treatment in SCA patients.
  
  
  METHODS
  The studied group was composed by 28 SCA patients. Thirteen of these patients were treated with HU and 15 of them were not. We used molecular methodology (PCR-RFLP) for hemoglobin S genotype confirmation and haplotypes identification. Biochemical parameters were measured using spectrophotometric methods (Thiobarbituric-acid-reactive substances and Trolox equivalent antioxidant capacity levels, catalase and GST activities) and plasma glutathione levels by High-performance liquid chromatography coupled to electrochemical detection.
  
  
  RESULTS
  We found the highest frequency of Bantu haplotype (48.2%) which was followed by Benin (32.1%). We observed also the presence of Cameroon haplotype, rare in Brazilian population and 19.7% of atypical haplotypes. The protective Hb F effect was confirmed in SCA patients because these patients showed an increase in Hb F levels that resulted in a 41.3% decrease on the lipid peroxidation levels (r =-0.74, p=0.01). Other biochemical parameters have not shown differential expression according to patient's haplotypes. Bantu haplotype presence was related to the highest lipid peroxidation levels in patients (p < 0,01), but it also conferred a differential response to HU treatment, raising Hb F levels in 52.6% (p = 0.03) when compared with the group with the same molecular profile without HU usage.
  
  
  CONCLUSIONS
  SCA patients with Bantu haplotype showed the worst oxidative status. However these patients also demonstrated a better response to the treatment with HU. Such treatment seems to have presented a "haplotype-dependent" pharmacological effect.
authors.affiliation: Department of Chemistry and Environmental Sciences, Sao Paulo State University-UNESP, Sao Paulo, Brazil. ealmeida@ibilce.unesp.br.
authors.forename: Danilo Grunig Humberto
authors.initials: DG
authors.lastname: Silva
authors.forename: Edis
authors.initials: E
authors.lastname: Belini Junior
authors.forename: Gisele Cristine de Souza
authors.initials: GC
authors.lastname: Carrocini
authors.forename: Lidiane de Souza
authors.initials: Lde S
authors.lastname: Torres
authors.forename: Octávio
authors.initials: O
authors.lastname: Ricci Júnior
authors.forename: Clarisse Lopes de Castro
authors.initials: CL
authors.lastname: Lobo
authors.forename: Claudia Regina
authors.initials: CR
authors.lastname: Bonini-Domingos
authors.forename: Eduardo Alves
authors.initials: EA
authors.lastname: de Almeida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005500:Follow-Up Studies; D005838:Genotype; D005978:Glutathione / Q000097:blood; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010641:Phenotype; D013053:Spectrophotometry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006451:Hemoglobin, Sickle; D005319:Fetal Hemoglobin; D005978:Glutathione; D006918:Hydroxyurea